This application requests support for the scientific meeting entitled, "1st International Costello Syndrome Research Symposium 2007". This meeting will be held on July 21, 2007 at the Marion L. Miller Auditorium at Doernbecher Children's Hospital, Oregon Health and Science University, Portland, OR. The principal investigator and co-director of this meeting is Katherine A. Rauen, Ph.D., M.D., of the University of California San Francisco. Organizational and content support will be provided by Ms. Lisa Schoyer, President of the Costello Syndrome Family Network (CSFN) and co-director of the research symposium, and Ms. Dawn Macready-Santos, CSFN Board Member and Chair of the 2007 CSFN meeting to be held concurrently with the research symposium. [unreadable] [unreadable] Costello syndrome (CS) is a complex developmental disorder involving characteristic craniofacial features, failure to thrive, developmental delay, cardiac and skeletal anomalies, and a predisposition to develop neoplasia, both benign and malignant. This symposium will focus on recent, exciting molecular advances in CS including the discovery of the causal gene, HRAS, as well as clinical research and future therapy options for this population of patients. For the first time, a solid foundation for the study of the genetic basis of Costello syndrome will allow basic science researchers and clinicians to begin to understand its pathogenesis. This, in turn, will lead to better treatment and possible therapy. The overall goal of this symposium is to provide an open forum for researchers, clinicians, and physician-scientists to share and discuss basic science and clinical issues setting forth a solid framework for future research, translational applications directed towards therapy and best practices for individuals with CS. Because of the wide phenotypic effect seen in children with CS, formalization of basic science and clinical research through this symposium will not only help gain insight into the cause and progression of cancer, but also into the understanding of how such a gene is involved in the regulation of normal human development. The specific aims of the meeting are 1) meet individuals with CS and learn of their capacities, 2) learn how causative mutations in HRAS alter protein function and how this alteration may contribute to the pathogenesis of CS, 3) inspire clinicians and clinical researchers to consider syndrome specific management of clinical issues, 4) inspire basics science researchers in the Ras and related fields to apply their basic science knowledge to the clinical aspects of CS, 5) begin a formal discussion in the application of Ras pathway modulators as possible systemic therapy for CS individuals, and 6) inaugurate a commitment to research symposia to be an integral part to the bi-annual International Costello Syndrome Family Conferences. The participants are to include basic scientists in the fields of biochemistry, bioinformatics, and molecular genetics, as well as, clinical investigators from disciplines in dysmorphology, cardiology, endocrinology, neurology, oncology, and development. The audience will consist of clinicians, basic scientists, physician-scientists, advocate leaders, trainees, students and families, all of whom share an underlying interest in CS. Special attention will be paid to the involvement of junior investigators, trainees (medical/graduate students, post docs and fellows) and clinicians and scientists from underrepresented communities. [unreadable] [unreadable] [unreadable]